Controlled (living) radical polymerization approaches such as nitroxide-mediated polymerization (NMP)(1), atom transfer radical polymerization (ATRP)(2), and reversible addition-fragmentation chain transfer polymerization (RAFT)(3, 4) are known in the art for preparing polymers having relatively narrow molecular weight distributions and advanced architectures. Polymers can be derived from diverse monomers via RAFT polymerization in both organic and aqueous conditions (5-11). Polymers derived from such radical polymerization approaches can be telechelic polymers—with distinct α and ω functionalities. Polymer conjugates have been prepared from telechelic polymers via coupling to various moieties of interest (12-17).
Approaches for preparing end-functionalized polymers are known. For example, polymers having functionalized end groups have been prepared using ATRP by modifying the initiator (18, 19), or using RAFT by modifying the chain transfer agent (CTA). For example, RAFT CTA's are known with functional leaving groups, RL (16, 17, 20-23), or alternatively with functional activating groups, Z (24, 25). Post-polymerization functionalization of polymers is also known. For example, polymers prepared by radical polymerization using RAFT CTAs based on xanthates, dithioesters, dithiocarbamates and trithiocarbonates, can be reduced with primary amines (26-28) or NaBH4 (12, 13) to result in a thiol end group. Although conjugation to thiols have been described (11, 13, 14, 26, 29-35) such reactions typically involve undesirable reaction conditions. U.S. Pat. No. 6,919,409 to Charmot et al. discloses ω-functionalization of RAFT polymers by chain extension with functionalized monomers; however, the disclosed approach includes cleavage of the thiocarbonylthio control transfer agent, thereby precluding further CTA-mediated radical polymerization, and thus limiting polymer architecture flexibility. Generally known approaches for preparing end-functional RAFT polymers are also limited with respect to certain functional groups such as amine functional groups. Moad et al., report for example that polymers with primary or secondary amine functionality cannot be prepared directly by RAFT polymerization, because these groups undergo facile reaction with thiocarbonylthio compounds. (See Moad et al., The Chemistry of Radical Polymerization, 2d Ed., p. 538-540 Elsevier (2006); See also WO 1998/001478). Indirect approaches using RAFT agents with latent (protected) amine functionality are known. (Id.)
Further approaches for preparing functionalized polymers such as ω-functionalized RAFT polymers are needed which overcome the various shortcomings of existing approaches.